It has long been known that calcium is a required nutriment for the human body. Not only does calcium enhance strong bones and teeth, but also in its carbonate salt form, it is useful in treating peptic ulcer disease. Moreover, several studies in the last few years have confirmed that post-menopausal women have a tendency toward osteoporosis, and thus need to take calcium.
Accordingly, calcium carbonate, one of the more readily available calcium salts has been widely used as a dietary supplement. Calcium carbonate is more acid soluble than other calcium salts, such as the saccharide salts. Furthermore, saccharides, for instance calcium gluconate, obviously have a lower amount of calcium per mole of calcium saccharide than is the case with calcium carbonate.
Some individuals have hypochlorhydria (low gastric secretion of acid), whereas others have achlorhydria (lack HCl in their gastric juice). Studies have shown that when these individuals swallow a calcium carbonate tablet, they simply excrete most of it instead of absorbing it. Such individuals are often diagnosed has having hypercalcemia because if the body lacks calcium, it will leave the bone tissue and circulate in the blood. Thus the blood has a measurable excess of calcium. It is believed that normal individuals, i.e. those who secrete acid in their gastrointestinal tract, easily absorb the calcium from calcium carbonate. Thus, researchers have postulated that individuals taking calcium carbonate orally apparently have to rely on their own gastrointestinal secretion of acid to convert this salt (which is insoluble in H.sub.2 O ) into a soluble form of calcium, namely, calcium chloride for adsorption by the body. See, for instance, "The Absorption of Calcium Carbonate", Annals of Internal Medicine, Vol. 66, No. 5, Ivanovich, Fellows, and Rich, Pages 917-923 (May, 1967).
If water insoluble calcium carbonate cannot be converted to the soluble calcium chloride form supposedly due to lack of acid in the individual's gastrointestinal tract, then the oral administration must be of a soluble form of calcium. One suggestion has been to have calcium carbonate present in a tablet comprising an effervescent system. Effervescent systems are well known and an example is ALKA-SELTZER PLUS % disclosed in U.S. Pat. No. 4,083,950. Such systems contain an effervescent couple which typically comprises an alkaline material, such as sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, and the like, together with an organic acid, such as citric acid, fumaric acid, adipic acid and the like. When the system is placed in water, the couple will react forming CO.sub.2 and a water soluble salt. Since calcium carbonate is related to the carbonates of sodium and potassium, the use of CaCO.sub.3 in an effervescent system seemed to be the obvious answer for providing a soluble form of calcium. Calcium carbonate was mixed with citric acid as an effervescent couple and the combination compressed into tablets. When these tablets were placed in water, they effervesced and there resulted an aqueous solution of soluble monocalcium citrate. See, for instance, Hunt and Johnson, "Relation Between Gastric Secretion of Acid and Urinary Excretion of Calcium After Oral Supplements of Calcium", Digestive Diseases and Sciences, Vol. 28, No. 5, Pages 417-421 (May, 1983). These authors deduced from the increased urinary output of calcium that when an individual drank this solution, the gastrointestinal tract readily absorbed the calcium which was now in the form of soluble monocalcium citrate.
However, problems have arisen with compressing these combination calcium carbonate/citric acid compositions into a stable, unitary tablet dosage form. Typically, calcium carbonate powder is blended with citric acid powder and a lubricant, and then the blend is charged directly to a tabletting press. However, difficulties arise when compacting these two components in admixture. In the presence of a little moisture, compacting the particles is facilitated as the water will act as a compression enhancing vehicle, but the water causes the two components to react as the two are stable (i.e. do not spontaneously react) only if kept substantially dry. It is well known to those skilled in the art that citric acid is incompatible with alkaline earth carbonates, such as calcium carbonate when water is present. (See Merck Index, 10th ed., (1983), page 2300). However, controlling moisture under manufacturing conditions is difficult. Moreover, as the moisture decreases, the "compression enhancing vehicle" effect of the water is lost and the particles tend not to stick during compacting. Of course, it is desired to have essentially no reaction until the tablet is placed into water just prior to ingestion.
Thus, to obviate instability in a unitary formulation, the two components may be physically separated from each other. In such compositions, some means is used to keep the active ingredients in the composition from contacting one another, such as film-coating the active ingredients with a suitable protective material or stratifying (layering) the active ingredients. However, when it is desired to have an effervescent composition, these techniques are often counterproductive.
Therefore a viable agent that would enhance tabletting and substantially inhibit degradation, yet not interfere with effervescence, would be desirable for calcium carbonate/citric acid formulations.
The prior art shows various agents used to enhance tabletting. Staniforth in U.S. Pat. No. 4,349,542 discloses a tabletting process using various tabletting agents such as lactose and Emdex (a spray-crystalized, maltose-dextrose direct tabletting sugar, supplied by K&K-Greeff Fine Chemicals Ltd., Croydon, U.K., manufactured by Edward Mendell, New York, U.S.A.), and McSweeney in U.S. Pat. No. 4,384,005, discloses a process to make an unsweetened beverage tablet using various tabletting agents such as tapioca dextrin (A. E. Staley #950SR, Decatur, Ill.) and maltodextrin (Mor Rex 1918).
However, the prior art does not disclose or suggest agents that not only enhance compression but also alleviate the degradation problems attendant effervescent systems comprising calcium carbonate/citric acid tablets.